An experiment was conducted to test the hypothesis that inclusion of the direct fed microbial Clostridium butyricum in diets for weanling pigs will improve growth performance, systemic immune function, microbiota composition, and gut morphology in weaned pigs. A total of 275 newly weaned pigs (20 ± 2 d of age) with an average initial BW of 6.4 ± 0.8 kg were allotted to a randomized complete block design with 11 pens per treatment. Diets included a positive control diet containing Carbadox, a negative control diet without Carbadox, and three treatment diets in which 1,250 × 108 cfu/kg, 2,500 × 108 cfu/kg, or 3,500 × 108 cfu/kg of C. butyricum was added to the negative control diet. A two-phase feeding program was used (phase 1, 14 d; phase 2, 21 d). At the conclusion of the experiment (day 35), a blood sample was collected from one pig per pen (11 pigs per treatment) and this pig was then euthanized and digesta and tissues samples were collected. Results indicated that for the overall phase, pigs fed the positive control diet had greater (P < 0.05) ADG and ADFI and tended (P = 0.064) to have greater final BW than pigs fed the negative control diet. The ADG and G:F increased and then decreased as increasing doses of C. butyricum were included in the diet (quadratic, P < 0.05). The concentration of tumor necrosis factor-α was less (P < 0.05) in pigs fed the positive control diet compared with pigs fed the negative control diet or diets containing C. butyricum. Crypt depth tended (P = 0.08) to be less in pigs fed the negative control diet compared with pigs fed the positive control diet and villus height tended to increase as the doses of C. butyricum increased in the diets (quadratic, P = 0.08). Villus height also tended (P = 0.084) to be greater in pigs fed diets containing C. butyricum compared with pigs fed the positive control diet. Crypt depth increased as the dose of C. butyricum increased (quadratic, P < 0.05) and villus width at the bottom tended to increase (linear, P = 0.072) as the dose of C. butyricum increased in the diet. Alpha and beta diversity indices of ileal and colonic microbiota were not affected by diet. In conclusion, addition of 1,250 × 108 cfu/kg of C. butyricum, but not greater levels, to diets fed to weanling pigs increased growth performance and tended to increase villus height and crypt depth, but changes in the abundance of intestinal microbiota were not observed.